The present invention is concerned with improved carbapenem antibiotics characterized by having a monocyclic or bicyclic quaternary heteroarylalkylthio substituent in the 2-position. The heteroaryl portion of the substituent is further substituted with an acidic moiety.
Thienamycin is a known carbapenem, broad spectrum antibiotic of the formula: ##STR3## Other derivatives of A are also known. The present quaternary, monocyclic or bicyclic heteroarylalkylthio substituted carbapenems have an antibiotic spectrum similar to or better than A. The present carbapenems also exhibit reduced seizure potential, i.e., less tendency to produce convulsions, when compared to the N-formimidoyl and N-acetimidoyl derivatives of A, and to related quaternary, monocyclic or bicyclic heteroarylalkylthio substituted carbapenems that lack the additional acidic moiety in the heteroaryl group.
U.S. Pat. No. 4,552,696 (Kim and Misco) discloses carbapenem antibiotics having a 2-sidechain of the formula ##STR4## wherein a possible substituent of the heteroaryl group is carboxyl. However, this carboxyl substituent is only one of a vast number of other enumerated substituents, and no special significance of any kind is attached to it. Furthermore, the patent disclosure contains data relating to "Toxicity After Intracranial Administration to Mice" and thus demonstrates an awareness of the problem of convulsive potential. Yet, there is no appreciation that an acidic moiety in the heteroaryl group, which makes the carbapenem compound overall an anionic zwitterion, will uniformly confer a significantly reduced tendency to produce convulsions in the overall compound.